The overall goal of this project is a better understanding of the ultrastructural and chemical changes which characterize the development of human cataracts. The cause of fiber cell destruction, during the development of human cataracts, is a main aspect of the proposal. This would include an ultrastructural analysis of 1) the process of lens fiber cell disintegration as seen with S.E.M., T.E.M. and freeze-etch E.M., and 2) the formation of intercellular spaces, and the analysis of their contents with energy-dispersive X-ray analysis. A major effort will be made to correlate specific ultrastructural and chemical findings with the presence of specific lens opacities, classified according to established Cooperative Cataract Research Group procedures (C.C.R.G., NEI). The operating rooms are adjacent to Kresge Eye Institute, and cataractous lenses can be photographed within minutes of extraction. A systematic study of the normal human lens, obtained primarily through the Michigan Eye Bank located within the Kresge Eye Institute, is proposed as a basis of comparison with the cataractous lens. This would include a study of junctional complexes (gap junctions) and tight junctions as seen primarily with freeze-etch E.M.) and other surface structural characteristics (S.E.M. and T.E.M.) at specific, defined locations within the lens. The sulfur-phosphorus data obtained in this laboratory indicate that energy-dispersive X-ray analysis can be an effective tool in elemental analysis within specific structures of the lens. Correlation of the location of the phosphorus-containing material with ultra-structural characteristics, and the presence of opacities as seen in the C.C.R.G. light microscope stereophotographs may indicate, for example, whether the phosphorus-containing material is associated with plasma membrane fragments, and how it relates to lens opacities.